Timolol/ Brinzolamide

Registered South African indications:

• Open­ angle glaucoma
• Ocular hypertension

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Hypersensitivity to other beta blockers
• Hypersensitivity to sulphonamides
• Severe renal impairment
• Asthma or history thereof
• Severe chronic obstructive pulmonary disease
• Sinus bradycardia
• Sick sinus syndrome
• Sino-atrial block
• Second or third degree atrioventricular block not controlled with pacemaker
• Overt cardiac failure
• Cardiogenic shock
• Severe allergic rhinitis
• Hyperchloraemic acidosis

Cautions

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Hepatic impairment
• Cardiovascular disease
• Hypotension
• First degree heart block
• Severe peripheral circulatory disorders
• Myasthenia gravis
• Mild to moderate chronic obstructive pulmonary disease
• Spontaneous hypoglycaemia
• History of atopy 
• History of severe anaphylactic reaction
• Pseudoexfoliative glaucoma 
• Pigmentary glaucoma
• Narrow angle glaucoma 
• Corneal diseases
• Dry eye conditions
• Diabetes mellitus
• Corneal dystrophies
• Frequent use
• Prolonged use
• Concomitant use of soft contact lenses
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: opd

Decrease intraocular pressure in adult patients with open ­angle glaucoma
Ocular hypertension for whom monotherapy provides insufficient intraocular pressure reduction

Timolol/ Brinzolamide
5/10 (mg/ml)

• Ophthalmic (opd): Apply 1 drop into conjunctival sac of affected eye(s), 12hrly; Max: 2 drops/eye/24hrs

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If other ophthalmic agents used, administer at least 5 minutes apart

Not established for use in children below 18 years

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• FDA Pregnancy Category C (Timolol, Brinzolamide) 

Breastfeeding

• Caution; not recommended (Timolol, Brinzolamide) 

Renal Impairment

• Mild to moderate: Caution; no information available 
• Severe: Contraindicated

Hepatic Impairment

• Caution; no information available

Elderly

• No dose adjustment recommended

Central Nervous System Disorders

• Insomnia
• Depression
• Memory loss
• Apathy
• Depressed mood
• Nightmares
• Nervousness
• Dysgeusia
• Cerebral ischaemia
• Cerebrovascular accident
• Syncope
• Exacerbation of myasthenia gravis
• Somnolence
• Motor dysfunction
• Amnesia
• Paraesthesia
• Tremor
• Hypoaesthesia
• Ageusia
• Dizziness
• Headache
• Malaise
• Feeling jittery
• Irritability

Cardiovascular Disorders

• Decreased heart rate
• Cardiac arrest
• Cardiac failure
• Atrioventricular block
• Cardio-respiratory distress
• Angina pectoris
• Bradycardia
• Irregular heart rate
• Arrhythmia
• Palpitations
• Tachycardia
• Chest pain
• Oedema
• Hypotension
• Hypertension
• Increased blood pressure
• Raynaud's phenomenon
• Cold hands and feet

Respiratory Disorders

• Cough
• Oropharyngeal pain
• Rhinorrhoea
• Bronchospasm
• Dyspnoea
• Asthma
• Epistaxis
• Bronchial hyperactivity
• Throat irritation
• Nasal congestion
• Upper respiratory tract congestion
• Postnasal drip
• Sneezing
• Nasal dryness
• Nasopharyngitis
• Pharyngitis
• Sinusitis
• Rhinitis

Gastrointestinal Disorders

• Abdominal pain 
• Diarrhoea
• Dry mouth
• Nausea and vomiting
• Oesophagitis
• Dyspepsia
• Abdominal discomfort
• Stomach discomfort
• Frequent bowel movements
• Gastrointestinal disorder
• Oral hypoaesthesia
• Oral paraesthesia
• Flatulence

Hepatobiliary Disorders

• Abnormal liver function tests

Genitourinary Disorders

• Haematuria
• Renal pain
• Pollakiuria
• Erectile dysfunction
• Sexual dysfunction
• Decreased libido

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Increased blood potassium
• Increased blood lactate dehydrogenase
• Increased blood chloride

Musculoskeletal Disorders

• Myalgia
• Muscle spasms
• Arthralgia
• Back pain
• Pain in extremity

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Maculopapular rash
• Generalised pruritus
• Skin tightness
• Dermatitis
• Alopecia
• Psoriasiform rash or exacerbation of psoriasis
• Rash
• Erythema

Immune, Blood and Lymphatic System Disorders

• Decreased white blood cell count
• Decreased red blood cell count
• Anaphylaxis
• Anaphylactic shock
• Systemic allergic reactions 

Sensory Disorders

• Punctate keratitis
• Eye pain
• Eye irritation
• Keratitis
• Dry eye
• Vital dye staining of the cornea 
• Eye discharge
• Eye pruritus
• Foreign body sensation in eyes
• Ocular hyperaemia
• Conjunctival hyperaemia
• Corneal erosion
• Anterior chamber flare
• Photophobia
• Increased lacrimation 
• Scleral hyperaemia
• Erythema of eyelid
• Eyelid margin crusting
• Increased optic nerve cup/disc ratio
• Choroidal detachment following filtration surgery
• Keratopathy
• Corneal epithelium defect
• Corneal epithelium disorder
• Increased intraocular pressure
• Eye deposit
• Corneal staining
• Corneal oedema
• Decreased corneal sensitivity
• Conjunctivitis
• Meibomianitis
• Diplopia
• Glare
• Photopsia
• Visual impairment
• Pterygium
• Ocular discomfort
• Keratoconjunctivitis sicca
• Hypoaesthesia of the eye
• Scleral pigmentation
• Subconjunctival cyst
• Eye swelling
• Eye allergy
• Madarosis
• Eyelid disorder
• Eyelid oedema
• Ptosis
• Vertigo
• Tinnitus

• Beta blockers
• Oral carbonic anhydrase inhibitors
• CYP3A4 inhibitors
• Oral calcium channel blockers
• Antiarrhythmics
• Digitalis glycosides
• Parasympathomimetics
• Guanethidine
• Clonidine
• Adrenaline
• CYP2D6 inhibitors 
• Antidiabetic agents

None routine

Timolol
Timolol maleate is a non-selective beta-adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anaesthetic activity. It combines reversibly with the beta-adrenergic receptor, and this inhibits the usual biologic response that would occur with stimulation of that receptor. Timolol maleate reduces elevated and normal intraocular pressure whether or not associated with glaucoma and has little or no effect on accommodation or pupil size.

Brinzolamide
Brinzolamide is a highly specific, non-competitive, reversible carbonic anhydrase inhibitor. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure. 

COMBINATION PREPARATIONS

Brinzolamide/ Timolol

Eye drops (per ml) 10mg/5mg

• Azarga (Novartis South Africa) originator